Epilepsy affects approximately 50 million of people worldwide and 30% of them are resistant to drugs. Neuromodulation is becoming a key option in patients with drug-resistant epilepsy who are not feasible for resective surgery. Vagus nerve stimulation (VNS) is the most commonly used adjunctive neuromodulatory method in every patient aged 4 years and older who is unsuitable for resective surgery. It is a minimally invasive, non-teratogenic, extracranial pacemaker-like device which delivers electrical stimuli to the vagus nerve and desynchronize aberrant cerebral rhythms involved in epileptogenesis. In this review we approached the information and clinical data of VNS development history, clinical applications and possible mechanism of action. We will also review optimal stimulation parameters and information about closed and open loop devices. Vagus nerve stimulation is safe, efficient with no significant side effects and substantial cost-saving benefit, that also shows an important improvement in mood, behavior, cognition and quality of life. The overall responder rate was observed in more than 50% of patients. On the other hand, it is not clear which patients will respond to this method of treatment and why the response is not immediate, there are no available biomarkers or other features like age, sex, seizure type/epileptic syndrome to predict response to vagus nerve stimulation therapy. The VNS Therapy System continues to be an important prospect in the treatment of pharmacoresistant epilepsy, that requires further studies in order to ensure the most advantageous therapeutic response.